Encapsulation state of messenger RNA inside lipid nanoparticles

Mark L Brader; Sean J Williams; Jessica M Banks; Wong H Hui; Z Hong Zhou; Lin Jin

doi:10.1016/j.bpj.2021.03.012

Encapsulation state of messenger RNA inside lipid nanoparticles

Biophys J. 2021 Jul 20;120(14):2766-2770. doi: 10.1016/j.bpj.2021.03.012. Epub 2021 Mar 25.

Authors

Mark L Brader¹, Sean J Williams², Jessica M Banks², Wong H Hui³, Z Hong Zhou³, Lin Jin²

Affiliations

¹ Moderna, Inc., Cambridge, Massachusetts. Electronic address: mark.brader@modernatx.com.
² Moderna, Inc., Cambridge, Massachusetts.
³ Department of Microbiology, Immunology, and Molecular Genetics, Los Angeles, Los Angeles, California; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, California.

Abstract

Understanding the structure of messenger RNA (mRNA) lipid nanoparticles, and specifically the microenvironment of the mRNA molecules within these entities, is fundamental to advancing their biomedical potential. Here, we show that a permeating cationic dye, thionine, can serve as a cryogenic electron microscopy contrasting agent by binding selectively to encapsulated mRNA without disturbing lipid nanoparticle morphology. Cryo-electron microscopy images identify the mRNA location, revealing that mRNA may exist within solvent-filled cavities or may be substantially lipid associated.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cryoelectron Microscopy
Lipids*
Nanoparticles*
RNA, Messenger / genetics

Substances

Lipids
RNA, Messenger